Alcohol drinking and cigarette smoking are highly correlated with a greater preponderance of heavy smokers among alcoholics than among the general population suggesting a common mechanism in the conjoint abuse of both alcohol and cigarettes (nicotine). The purpose of this study is to establish a role for the endogenous opioid system in nicotine and alcohol dependence by evaluating the ability of the opioid antagonist naloxone, to precipitate withdrawal symptoms, similar to those seen in opiate withdrawal, in male and female, alcohol and nicotine dependent individuals and normal subjects. To date 48 subjects (smokers, alcoholic smokers, alcoholics and nonsmokers) have participated in the study. Smokers experienced greater dose-related increases in total Clinical Institute for Narcotic Assessment Scale(CINA) scores, specifically in withdrawal symptoms such as nervousness, restlessness, muscle tension, feeling hot/cold, gooseflesh, sweating and nasal congestion, compared with nonsmokers. The contribution of alcohol dependence to opiate withdrawal symptoms was also tested in 7 alcohol dependent subjects (>25 drinks/week) who were smokers/nonsmokers. Alcoholic smokers also experienced withdrawal symptoms but they appear to be less severe than the symptoms seen in nonalcoholic smokers. These results provide further support for opioid involvement in nicotine dependence. We plan to continue recruiting alcohol and nicotine, dependent and non-dependent subjects and will hope to run 20-30 subjects for the next grant year.